Author(s) from Durham

Abstract

Nesprins form a novel class of nuclear envelope-anchored
spectrin-repeat proteins. We show that a direct association
of their highly conserved C-terminal luminal domain with
the inner nuclear membrane protein Sun1 mediates their
nuclear envelope localisation. In Nesprin-1 and Nesprin-2
the conserved C-terminal amino acids PPPX are essential
for the interaction with a C-terminal region in Sun1. In
fact, Sun1 is required for the proper nuclear envelope
localisation of Nesprin-2 as shown using dominant-negative
mutants and by knockdown of Sun1 expression. Sun1 itself
does not require functional A-type lamins for its
localisation at the inner nuclear membrane in mammalian
cells. Our findings propose a conserved nuclear anchorage
mechanism between Caenorhabditis elegans and mammals
and suggest a model in which Sun1 serves as a ‘structural
bridge’ connecting the nuclear interior with the actin
cytoskeleton.